Sertaconazole (WHO-INN) is an antifungal agent broadly used in the therapy of infections caused by fungi and yeasts in man and animals. Sertaconazole refers to 1-[2-(7-chlorobenzo[b]thiophene-3-yl-methoxy)-2-(2,4-dichloro-phenyl)ethyl]-1H-imidazole. Commonly sertaconazole is used as mononitrate salt (I).
The specification EP 151477 discloses the preparation of sertaconazole mononitrate (I) by reacting 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)-ethanol (II) with sodium hydride and 3-bromomethyl-7-chlorobenzo[b]thiophene (III) in hexamethylphosphoramide (HMPA) and treating the resulting sertaconazole free base with nitric acid.
The specification CN 1358719 (CAPLUS 2003:711267) discloses the synthesis of sertaconazole mononitrate (I) by etherifying 3-bromomethyl-7-chlorobenzo[b]thiophene (III) with 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)-ethanol (II) at a molar ratio of 1:1 in toluene-water (3:1, v/v) in the presence of sodium hydroxide and 50% tetrabutylammonium chloride (IV, Z═Cl) solution at 80° C. for 4 hours, extracting with ethyl ether to obtain free base of sertaconazole, salifying with nitric acid and recrystallizing in 95% ethanol. The resulting content in sertaconazole mononitrate of the thus prepared product is >98.5%.
Molecular formulas for compounds (I)-(IV) and sertaconazole mononitrate monohydrate (V) are shown in FIG. 1/5.